A thrombus is the inappropriate activation of the hemostatic process in an uninjured or slightly injured vessel. A thrombus in a large blood vessel (mural thrombus) will decrease blood flow through that vessel. In a small blood vessel (occlusive thrombus), blood flow may be completely cut-off resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is termed as an embolus.
Some of the conditions which elevate risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack, extended periods of inactivity (see deep venous thrombosis below), and genetic or disease-related deficiencies in the blood's clotting abilities.
Blood clot prevention and treatment reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing thrombi; they are able to decrease blood coagulation by inhibiting vitamin K epoxide reductase, an enzyme needed to form mature clotting factors.
Acute ischemic stroke (AIS) is a potentially devastating disease that goes untreated in greater than 95% of patients. Acute ischemic stroke is estimated to affect more than 700,000 patients each year in the USA and 15 million worldwide [1,2]. New pharmacological therapeutics that can reduce the clinical deficits associated with AIS are needed. Ischemic stroke results from an obstruction within a blood vessel supplying blood to the brain.
Hemorrhagic stroke accounts for about 17 percent of stroke cases. It occurs when a weakened blood vessel ruptures.
Tissue plasminogen activator (tPA) is a protein thrombolytic agent (clot-busting drug). It is approved for use in certain patients having a heart attack or stroke. The drug can dissolve blood clots, which cause most heart attacks and strokes. tPA is the only drug approved by the U.S. Food and Drug Administration for the acute (urgent) treatment of ischemic stroke. Specifically, it is approved for the treatment of ischemic stroke in the first three hours after the start of symptoms [3].
If given promptly, tPA can significantly reduce the effects of ischemic stroke and reduce permanent disability. However, a time delay in starting tPA treatment often occurs because, when a patient presents with stroke-like symptoms, it is not immediately apparent whether the stroke has been caused by blood clots (ischemic stroke) or by a ruptured blood vessel (hemorrhagic stroke). tPA can only be given for ischemic strokes; therefore, the type of stroke must be determined before tPA is administered.
Although over 80% of all strokes are ischemic strokes, tPA or any thrombolytic, cannot be given immediately since it is possible that it could cause the hemorrhagic strokes to produce even worse effects. Determining whether a given patient has suffered a hemorrhagic or ischemic stroke is a time-consuming diagnosis which stands as a “gate” to immediate treatment. That, coupled with the fact that tPA must be given within 3 hours of the first symptoms, has resulted in only a small fraction of stroke patients receiving tPA.
tPA is effective in numerous preclinical models of acute ischemic stroke including the rabbit small clot embolic stroke model (RSCEM), [4] a useful tool and possibly a predictor of effective treatments that may eventually translate into functional efficacy in human clinical trials [2,4-7]. The primary endpoint used when assessing treatment efficacy in the RSCEM is functional behavior, which is based upon motor function components of the National Institute of Health Stroke Scale (NIHSS) for stroke in humans [8, 9].
Cerebral edema is the presence of excess fluid within either the cells or the extracellular spaces of the brain. This disorder also causes brain swelling and a rise in intracranial pressure. Head injuries, encephalitis, abscesses, lack of oxygen, tumors, strokes, and toxic agents are the most common causes of cerebral edema. Current treatment approaches to cerebral edema can include mannitol, diuretics and corticosteroids. One of the main corticosteroids used is dexamethasone (Decadron).
Carotenoids are a class of hydrocarbons consisting of isoprenoid units. The backbone of the molecule consists of conjugated carbon-carbon double and single bonds, and can have pendant groups. Carotenoids such as crocetin and trans sodium crocetinate (TSC) are known to increase the diffusivity of oxygen in water.
U.S. Pat. No. 6,060,511 relates to trans sodium crocetinate (TSC) and its uses. The patent covers various uses of TSC such as improving oxygen diffusivity and treatment of hemorrhagic shock.
U.S. patent application Ser. No. 10/647,132 relates to synthesis methods for making bipolar trans carotenoids (BTC), including bipolar trans carotenoid salts (BTCS), and methods of using them.
U.S. patent application Ser. No. 11/361,054 relates to improved BTC synthesis methods and novel uses of the BTC.
U.S. patent application Ser. No. 12/081,236 relates to the use of bipolar trans carotenoids as a pretreatment and in the treatment of peripheral vascular disease.
U.S. application Ser. No. 12/289,713 relates to a new class of therapeutics that enhance small molecule diffusion.